Single-cell transcriptome profiling identifies the activation of type I interferon signaling in ossified posterior longitudinal ligament.

IF 3.9 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Xiao Liu, Lei Zhang, Ge Wang, Wei Zhao, Chen Liang, Youzhi Tang, Yenan Fu, Bo Liu, Jing Zhang, Xiaoguang Liu, Hongquan Zhang, Yu Yu
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引用次数: 0

Abstract

Ossification of the posterior longitudinal ligament (OPLL) is a condition comprising ectopic bone formation from spinal ligaments. This disease is a leading cause of myelopathy in the Asian population. However, the molecular mechanism underlying OPLL and efficient preventive interventions remain unclear. Here, we performed single-cell RNA sequencing and revealed that type I interferon (IFN) signaling was activated in the ossified ligament of patients with OPLL. We also observed that IFN-β stimulation promoted the osteogenic differentiation of preosteoblasts in vitro and activated the ossification-related gene SPP1, thereby confirming the single-cell RNA sequencing findings. Further, blocking the IFN-α/β subunit 1 receptor (IFNAR1) using an anti-IFNAR1 neutralizing antibody markedly suppressed osteogenic differentiation. Together, these results demonstrated that the type I IFN signaling pathway facilitated ligament ossification, and the blockade of this signaling might provide a foundation for the prevention of OPLL.

单细胞转录组分析确定了骨化后纵韧带中 I 型干扰素信号的激活。
后纵韧带骨化症(OPLL)是一种由脊柱韧带异位骨形成的疾病。这种疾病是亚洲人脊髓病的主要病因。然而,OPLL 的分子机制和有效的预防干预措施仍不清楚。在此,我们进行了单细胞 RNA 测序,发现 OPLL 患者骨化韧带中的 I 型干扰素(IFN)信号被激活。我们还观察到,IFN-β刺激可促进体外前成骨细胞的成骨分化,并激活骨化相关基因SPP1,从而证实了单细胞RNA测序的结果。此外,使用抗 IFNAR1 中和抗体阻断 IFN-α/β 亚基 1 受体(IFNAR1)可明显抑制成骨分化。这些结果共同表明,I型IFN信号通路促进了韧带骨化,而阻断这种信号通路可能为预防OPLL奠定基础。
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来源期刊
Frontiers of Medicine
Frontiers of Medicine ONCOLOGYMEDICINE, RESEARCH & EXPERIMENTAL&-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
18.30
自引率
0.00%
发文量
800
期刊介绍: Frontiers of Medicine is an international general medical journal sponsored by the Ministry of Education of China. The journal is jointly published by the Higher Education Press and Springer. Since the first issue of 2010, this journal has been indexed in PubMed/MEDLINE. Frontiers of Medicine is dedicated to publishing original research and review articles on the latest advances in clinical and basic medicine with a focus on epidemiology, traditional Chinese medicine, translational research, healthcare, public health and health policies.
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